Numerous potentially effective therapeutic agents often exhibit poor bio-pharmaceutical properties. This problem, which can preclude the effective oral use of a potential therapeutic agent, is generally targeted with analog methodology, screening ligands, for the biopharmaceutical properties of permeability and metabolism. However, this approach can lead to less desirable drug candidates because properties that optimize biopharmaceutical properties of a molecule may not be the properties or structure that optimize its ligand binding and ultimate efficacy.
A problem associated with rendering a poorly soluble therapeutic agent orally bioavailable is that the transport and release of the active agent from a transport species are unpredictable. Amino acid and peptide transporters and identification of cells having amino acid and peptide transporter activity are known in the art. For example, PEPT1 and/or PEPT2 are known transporters as described in references [29]-[36]. Yet a robust delivery prodrug actively transported into cells bearing PEPT1 and/or PEPT2 transport receptors has remained elusive.
Thus, there exists a need for novel bioavailable drug compositions and processes for synthesis and therapeutic use of the same.